crossing96/oncoscreening huggingface dataset:
Rapid geriatric screening tools predict inability to manage stoma by oneself after urinary diversion: G8 and IADL-modified G8.	INTRODUCTION: This study aimed to evaluate whether functional screening, as assessed by the Geriatric-8 (G8) and the instrumental activities of daily living (IADL)-modified G8, are associated with the inability to manage a stoma by themselves in patients with bladder cancer who underwent robot-assisted radical cystectomy. MATERIALS AND METHODS: We analyzed a total of 110 consecutive patients with bladder cancer who underwent robot-assisted radical cystectomy and were screened preoperatively using the G8 and the IADL-modified G8 at our institution between January 2020 and December 2022. Patients who could not undergo geriatric screening at the preoperative clinic before surgery and patients who underwent orthotopic neobladder construction were excluded. We evaluated the association between clinical factors, including scores of G8 and IADL-modified G8, and the inability to manage a stoma by oneself. For both G8 and IADL-modified G8, a cutoff value of ≤14 was set. RESULTS: Of the 110 patients, the median age was 77 years, 92 (84%) patients were male and 47 (43%) patients were unable to manage a stoma by themselves. The geriatric assessment indicated that 64 patients (58%) were classified in the low G8 (≤14) group and 66 patients (60%) were classified in the low IADL-modified G8 (≤14) group. The values of area under the receiver operating characteristic curve for predicting inability to manage stoma by oneself were 0.725 for the G8 and 0.734 for the IADL-modified G8, respectively. Multivariate analysis including the G8 revealed that age ≥ 80, Charlson comorbidity index of ≥3, and G8 ≤ 14 (odds ratio [OR] = 4.9; 95% confidence interval [CI] = 1.8-13.0; P = 0.002) were independent risk factors for inability to manage a stoma by oneself. Likewise, multivariate analysis including the IADL-modified G8 revealed that age ≥ 80, Charlson comorbidity index of ≥3, and IADL-modified G8 ≤ 14 (OR = 5.4; 95% CI = 1.9-14.0; P = 0.001) were independent risk factors for inability to manage a stoma by oneself. DISCUSSION: Screening using G8 and IADL-modified G8 may predict patients who have difficulty self-managing their stomas.	bladder
Regulation of CD8(+) T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer.	The limited success of immunotherapies targeting immune checkpoint inhibitors is largely ascribed to the lack of infiltrating CD8(+) T lymphocytes. Circular RNAs (circRNAs) are a novel type of prevalent noncoding RNA that have been implicated in tumorigenesis and progression, while their roles in modulating CD8(+) T cells infiltration and immunotherapy in bladder cancer have not yet been investigated. Herein, we uncover circMGA as a tumor-suppressing circRNA triggering CD8(+) T cells chemoattraction and boosting the immunotherapy efficacy. Mechanistically, circMGA functions to stabilize CCL5 mRNA by interacting with HNRNPL. In turn, HNRNPL increases the stability of circMGA, forming a feedback loop that enhances the function of circMGA/HNRNPL complex. Intriguingly, therapeutic synergy between circMGA and anti-PD-1 could significantly suppress xenograft bladder cancer growth. Taken together, the results demonstrate that circMGA/HNRNPL complex may be targetable for cancer immunotherapy and the study advances our understanding of the physiological roles of circRNAs in antitumor immunity.	bladder
Cxbladder Monitor testing to reduce cystoscopy frequency in patients with bladder cancer.	PURPOSE: Bladder cancer surveillance is associated with high costs and patient burden. CxMonitor (CxM), a home urine test, allows patients to skip their scheduled surveillance cystoscopy if CxM-negative indicating a low probability of cancer presence. We present outcomes from a prospective multi-institutional study of CxM to reduce surveillance frequency during the coronavirus pandemic. MATERIALS AND METHODS: Eligible patients due for cystoscopy from March-June 2020 were offered CxM and skipped their scheduled cystoscopy if CxM-negative. CxM-positive patients came for immediate cystoscopy. The primary outcome was safety of CxM-based management, assessed by frequency of skipped cystoscopies and detection of cancer at immediate or next cystoscopy. Patients were surveyed on satisfaction and costs. RESULTS: During the study period, 92 patients received CxM and did not differ in demographics nor history of smoking/radiation between sites. 9 of 24 (37.5%) CxM-positive patients had 1 T0, 2 Ta, 2 Tis, 2 T2, and 1 Upper tract urothelial carcinoma (UTUC) on immediate cystoscopy and subsequent evaluation. 66 CxM-negative patients skipped cystoscopy, and none had findings on follow-up cystoscopy requiring biopsy. Six of these patients did not attend follow-up, 4 elected to undergo additional CxM instead of cystoscopy, 2 stopped surveillance, and 2 died of unrelated causes. CxM-negative and positive patients did not differ in demographics, cancer history, initial tumor grade/stage, AUA risk group, or number of prior recurrences. Median satisfaction (5/5, IQR 4-5) and costs (26/33, 78.8% no out-of-pocket costs) were favorable. CONCLUSIONS: CxM safely reduces frequency of surveillance cystoscopy in real-world settings and appears acceptable to patients as an at-home test.	bladder
Aristolochic acid induces an inflammatory response with prostaglandin E2 production and apoptosis in NRK-52E proximal tubular cells.	Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy in which ingestion of aristolochic acid (AA) causes acute kidney injury, with progressive renal fibrosis and upper urothelial carcinoma. Although the pathological features of AAN have been reported to involve significant cell degeneration and loss in the proximal tubules, the details of the toxic mechanism in the acute phase of the disease remain unclear. This study investigates the cell death pathway and intracellular metabolic kinetics of AA exposure in rat NRK-52E proximal tubular cells. AA exposure induces dose- and time-dependent apoptotic cell death in NRK-52E cells. We examined the inflammatory response to further investigate the mechanism of AA-induced toxicity. AA exposure increased the gene expression of inflammatory cytokines IL-6 and TNF-α, suggesting that AA exposure induces inflammation. Furthermore, analysis of lipid mediators by LC-MS revealed increases in intra- and extra-cellular arachidonic acid and prostaglandin E2 (PGE2). To investigate the relationship between the AA-induced increase in PGE2 production and cell death, celecoxib, an inhibitor of cyclooxygenase-2 (COX-2), which is involved in the production of PGE2, was administered, and a marked inhibition of AA-induced cell death was observed. These results suggest that exposure to AA induces concentration- and time-dependent apoptosis in NRK-52E cells, which is attributed to inflammatory responses mediated by COX-2 and PGE2.	bladder
CDCP1 (CUB domain containing protein 1) is a potential urine-based biomarker in the diagnosis of low-grade urothelial carcinoma.	Urine-based cytology is non-invasive and widely used for clinical diagnosis of urothelial carcinoma (UC), but its sensitivity is less than 40% for low-grade UC detection. As such, there is a need for new diagnostic and prognostic biomarkers of UC. CUB domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein highly expressed in various cancers. Using tissue array analysis, we demonstrated that CDCP1 expression in UC patients (n = 133), especially in those with low-grade UC, was significantly higher than in 16 normal persons. In addition, CDCP1 expression in urinary UC cells could also be detected by using immunocytochemistry method (n = 11). Furthermore, in 5637-CD cells, overexpression of CDCP1 affected the expression of epithelial mesenchymal transition-related markers and increased matrix metalloproteinase 2 expression and migration ability. Conversely, the knockdown of CDCP1 in T24 cells had the opposite effects. Using specific inhibitors, we demonstrated the involvement of c-Src/PKCδ signaling in the CDCP1-regulated migration of UC. In conclusion, our data suggest that CDCP1 contributes to the malignant progression of UC and may have the potential as a urine-based biomarker for detecting low-grade UC. However, a cohort study needs to be conducted.	bladder
Plasmacytoid urothelial carcinoma - A clinicopathological case series of an aggressive variant of urothelial cancer.	BACKGROUND: Many new morphological variants of urothelial carcinoma of urinary bladder have been described in the literature, plasmacytoid/signet ring cell/diffuse variant being one of the rare amongst these. Till date, no case series has been reported from India, describing this variant. MATERIALS AND METHODS: We retrospectively analyzed the clinicopathological data of 14 patients diagnosed at our center with plasmacytoid urothelial carcinoma. RESULTS: Seven cases (50%) were pure forms while the remaining 50% of cases had a concurrent conventional urothelial carcinoma component. Immunohistochemistry was performed to rule out other mimickers of this variant. Treatment-related data were available for seven patients, while follow-up was available for nine cases. CONCLUSION: Overall, plasmacytoid variant of urothelial carcinoma is considered to be an aggressive tumor with poor prognosis.	bladder
Upper Tract Urinary Carcinoma: A Unique Immuno-Molecular Entity and a Clinical Challenge in the Current Therapeutic Scenario.	Urothelial carcinoma (UC) is the most frequent malignancy of the urinary tract, which consists of bladder cancer (BC) for 90%, while 5% to 10%, of urinary tract UC (UTUC). BC and UTUC are characterized by distinct phenotypical and genotypical features as well as specific gene- and protein- expression profiles, which result in a diverse natural history of the tumor. With respect to BC, UTUC tends to be diagnosed in a later stage and displays poorer clinical outcome. In the present review, we seek to highlight the individuality of UTUC from a biological, immunological, genetic-molecular, and clinical standpoint, also reporting the most recent evidence on UTUC treatment. In this regard, while the role of surgery in nonmetastatic UTUC is undebated, solid data on adjuvant or neoadjuvant chemotherapy are still an unmet need, not permitting a definite paradigm shift in the standard treatment. In advanced setting, evidence is mainly based on BC literature and retrospective studies and confirms platinum-based combination regimens as bedrock of first-line treatment. Recently, immunotherapy and target therapy are gaining a foothold in the treatment of metastatic disease, with pembrolizumab and atezolizumab showing encouraging results in combination with chemotherapy as a first-line strategy. Moreover, atezolizumab performed well as a maintenance treatment, while pembrolizumab as a single agent achieved promising outcomes in second-line setting. Regarding the target therapy, erdafitinib, a fibroblast growth factor receptor inhibitor, and enfortumab vedotin, an antibody-drug conjugate, proved to have a strong antitumor property, likely due to the distinctive immune-genetic background of UTUC. In this context, great efforts have been addressed to uncover the biological, immunological, and clinical grounds in UTUC patients in order to achieve a personalized treatment.	bladder
RNA-seq reveals novel mechanistic targets of Livin in bladder cancer.	BACKGROUND: Bladder cancer is a very common malignancy with a high recurrence rate. The survival of patients with muscle-invasive bladder cancer is poor, and new therapies are needed. Livin has been reported to be upregulated in bladder cancer and influence the proliferation of cancer cells. MATERIALS AND METHODS: The Livin gene in human bladder cancer cell line T24 was knocked out, and the differentially expressed genes were identified by RNA-seq and qPCR. RESULTS: Livin knockdown affects gene expression and has strong negative effects on some cancer-promoting pathways. Furthermore, combined with bladder cancer clinical sample data downloaded from TCGA and GEO, 2 co-up-regulated genes and 58 co-down-regulated genes were identified and validated, which were associated with cancer proliferation and invasion. CONCLUSION: All these results suggest that Livin plays an important role in bladder cancer and could be a potential anticancer target in clinical therapy.	bladder
First-line Chemotherapy Response Is Associated With Clinical Outcome During Immune Checkpoint Inhibitor Treatment in Advanced Urothelial Carcinoma: A Real World Retrospective Study.	BACKGROUND/AIM: Immune checkpoint inhibitors (ICI) have become important tools for the treatment of advanced urothelial carcinoma (aUC). However, the clinical strategy using ICIs and chemotherapy is still controversial. The aim of this study was to evaluate the association of clinical parameters in aUC patients with ICI treatment. PATIENTS AND METHODS: We retrospectively analyzed aUC patients who received atezolizumab and pembrolizumab between January 2015 and October 2020. The associations between baseline demographics and clinical outcomes were evaluated. RESULTS: Of the 74 included patients, the median age was 67 years. Among them, 53 patients received atezolizumab and 21 received pembrolizumab. There were 50 patients receiving first line ICIs therapy and 24 receiving second line monotherapy. Fifty-two (83.87%, 52/62) received cisplatin among all chemotherapy patients. The median progression free survival was 10.94 months, and the overall survival was 28.44 months. Poor chemotherapy response or no chemotherapy, liver metastases, Eastern Cooperative Oncology Group (ECOG) status and higher neutrophil/lymphocyte ratio (NLR) were associated with higher risk of disease progression (HR=5.70, 95% CI=2.04-15.90, p=0.001; HR=6.08, 95% CI=1.79-20.57, p=0.004; HR=5.40, 95% CI=1.76-16.57, p=0.003; HR=6.08, 95% CI=2.56-14.44, p<0.001 and HR=1.02, 95% CI=1.01-1.03, p=0.002, respectively). Liver metastases and WBC before ICI were associated with increased risk of death (HR=11.95, 95% CI=3.22-44.34, p<0.001; HR=1.0001, 95%=CI=1.00001-1.00002, p=0.036 respectively) while ICI response was associated with decreased death (HR=0.22, 95%CI=0.08-0.62, p=0.004). Chemotherapy response was associated with better ICI treatment response (OR=6.52, 95% CI=1.45-29.24, p=0.014) while lymph node metastases and poor ECOG status were associated with poor ICI response (OR=0.31, 95% CI=0.10-0.94, p=0.038; OR=0.32, 95% CI=0.11-0.95, p=0.040). CONCLUSION: Our real-world data show a predictive role of first-line chemotherapy response to ICI treatment efficacy in aUC patients as well as other prognostic factors, such as ECOG status, serum WBC or NLR and liver metastases.	bladder
The role of smoking in explaining racial/ethnic disparities in bladder cancer incidence in the United States.	INTRODUCTION: Smoking is the most important modifiable risk factor for bladder cancer (BC), with the odds of developing BC among current and former smokers 3 times higher than never-smokers. We hypothesized that the observed disparities in BC incidence may be partially attributable to differences in smoking prevalence. We examined the attributable risk of BC related to smoking according to race/ethnicity and sex. MATERIAL AND METHODS: We used data from SEER and the Behavioral Risk Factor Surveillance System to estimate BC cases that would have been prevented if current and former smokers had never smoked to calculate the Population Attributable Fractions, stratified by sex and race/ethnicity. SDs of BC incidences across racial/ethnic groups before and after smoking elimination were calculated to estimate disparities. RESULTS: A total of 25,747 cases of BC were analyzed from 21 registries in 2018. By removing smoking, 10,176 cases (40%) would have been eliminated. Smoking was associated with a higher proportion of BC cases among males (42%) than females (36%). Across racial/ethnic groups, smoking contributed to the highest proportion of BC cases among American Indian/Alaska Natives (AI/AN) (43%) and Whites (36%) for females, and highest among AI/ANs (47%) and Blacks (44%) for males. Removing smoking, the SD of BC incidence across racial/ethnic groups was reduced for females (39%) and males (44%). CONCLUSION: Approximately 40% of cases of BC in the United States are attributable to smoking, with the highest proportion in AI/ANs for both males and females, and the lowest in Hispanics for females and Asians and Pacific Islanders for males. Smoking contributes to almost half of racial/ethnic disparities in BC incidence in the United States. Accordingly, health policy to encourage smoking cessation among racial-ethnic minorities may substantially reduce inequalities in BC incidence.	bladder
Open vs robotic intracorporeal Padua ileal bladder: functional outcomes of a single-centre RCT.	"PURPOSE: Functional outcomes of robot-assisted (RA) radical cystectomy (RC) with intracorporeal orthotopic neobladder (i-ON) have been poorly investigated. The study aimed to report functional outcomes of a prospective randomized controlled trial (RCT) comparing open RC (ORC) and RARC with i-ON. METHODS: Inclusion criteria were cT2-4/N0/M0, or BCG-failure high-grade urothelial carcinoma, candidate to RC with curative intent. A covariate adaptive randomization process was used, based on the following variables: BMI, ASA score, haemoglobin levels, cT-stage, neoadjuvant chemotherapy, urinary diversion. Day-time continence was defined as ""totally dryness"", nigh-time continence as pad wetness ≤ 50 cc. Continence recovery probabilities were compared between arms with Kaplan-Meier method and Cox regression analysis was performed to identify predictors of continence recovery. HRQoL outcomes analysis was assessed with a generalized linear mixed effect regression (GLMER) model. RESULTS: Out of 116 patients randomized, 88 received ON. Quantitative analysis of functional outcomes reported similar results in terms of day continence, while a better night continence status in ORC cohort was observed. However, 1-yr day- and night-time continence recovery probabilities were comparable. Night-time micturition frequency < 3 h was the only predictor of nigh-time continence recovery. At GLMER, 1-yr body image and sexual functioning were significantly better in RARC cohort, while urinary symptoms were comparable between arms. CONCLUSION: Despite superiority of ORC at quantitative night-time pad use analysis, we showed comparable day- and night-time continence recovery probabilities. At 1-yr analysis of HRQoL outcomes, urinary symptoms were comparable between arms, while RARC patients reported lower body image and sexual functioning worsening."	bladder
Case report: Urothelial carcinoma of the renal pelvis with trophoblastic differentiation: A rare case report and review of literature.	We report a rare case of urothelial carcinoma (UC) of the renal pelvis with trophoblastic differentiation that occurred in a 55-year-old male patient. The patient presented with gross hematuria and paroxysmal lumbago pain 5 months ago. The enhanced computed tomography (CT) scan demonstrated a large space occupying lesion in the left kidney and multiple retroperitoneal lymph node enlargements. Histologically, high-grade infiltrating urothelial carcinoma (HGUC) contained giant cells which were positive for beta-human chorionic gonadotropin (β-hCG). Three weeks after resection, positron emission tomography and computed tomography (PET-CT) scan showed multiple nodules of metastasis in the left renal region, extensive systemic muscle, bone, lymph node, liver and bilateral lung metastases. The patient underwent bladder perfusion chemotherapy and gemcitabine combined with cisplatin chemotherapy regimens. This is the eighth documented case of UC of the renal pelvis with trophoblastic differentiation. Due to its rarity and extremely poor prognosis, it is important to clarify the characteristics of the disease and make an accurate and prompt diagnosis.	bladder
A novel microfluidic system for enrichment of functional circulating tumor cells in cancer patient blood samples by combining cell size and invasiveness.	A highly invasive subpopulation of circulating tumor cells (CTCs) may constitute seeds for metastases, which are therefore considered functional CTCs. However, there are few effective strategies to detect CTCs based on invasive phenotypes. Herein, we focused on functional CTCs with high invasiveness and designed an integrated microfluidic system to differentiate the invasive potential of CTCs for more accurate metastasis prediction. By combining size-based enrichment and invasiveness-based analysis, the system managed to continuously remove most hemocytes by 8 μm gaps and analyze the invasiveness of the enriched CTCs by Matrigel loading. In addition to a device, a single pump and a Petri dish were included to provide an FBS gradient for driving cell invasion and maintain a long-term cell culture. The system successfully identified functional CTCs derived from different types of cancer patients, including colorectal, kidney and bladder cancer patients, using whole blood without any sample pretreatment process. Within 28 cases of colorectal cancer patients, functional CTCs were detected in 61.54% of patients with metastases, along with stronger invasiveness evaluated by migration/invasion distance than those from patients without metastases (P < 0.05). Furthermore, one bladder cancer patient was diagnosed with recurrence six months after detection, indicating the excellent value for cancer metastases prediction. In addition, great phenotypic heterogeneity of CTCs was also observed at the single-cell level, including invasion, proliferation and dormancy, which provided an effective strategy for metastasis prediction based on CTC function as a single cell.	bladder
Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade.	Bladder cancer (BC) is one of the most prevalent cancers worldwide. However, the recurrence rate and five-year survival rate have not been significantly improved in advanced BC, and new therapeutic strategies are urgently needed. The anticancer activity of stellettin B (SP-2), a triterpene isolated from the marine sponge Rhabdastrella sp., was evaluated with the MTT assay as well as PI and Annexin V/7-AAD staining. Detailed mechanisms were elucidated through an NGS analysis, protein arrays, and Western blotting. SP-2 suppressed the viability of BC cells without severe toxicity towards normal uroepithelial cells, and it increased apoptosis with the activation of caspase 3/8/9, PARP, and γH2AX. The phosphorylation of FGFR3 and its downstream targets were downregulated by SP-2. Meanwhile, it induced autophagy in BC cells as evidenced by LC3-II formation and p62 downregulation. The inhibition of autophagy using pharmacological inhibitors or through an ATG5-knockout protected RT-112 cells from SP-2-induced cell viability suppression and apoptosis. In addition, the upregulation of DAPK2 mRNA and protein expression also contributed to SP-2-induced cytotoxicity and apoptosis. In RT-112 cells, an FGFR3-TACC3-knockout caused the downregulation of DAPK2, autophagy, and apoptosis. In conclusion, this is the first study demonstrating that SP-2 exhibits potent anti-BC activity by suppressing the FGFR3-TACC3/Akt/mTOR pathway, which further activates a novel autophagy/DAPK2/apoptosis signaling cascade.	bladder